Equilibrium Radioligand Displacement | Competition Association Binding | ||||||||
---|---|---|---|---|---|---|---|---|---|
Ligand | pKIa (95% CI) | pKBb (95% CI) | Log αc (95% CI) | n | kon [×106 (M−1min−1)]d (95% CI) | koff (min−1)e (95% CI) | RTf | pKDg | n |
min | |||||||||
MPPA | 6.51 (6.25–6.77) | n.d. | n.d. | 4 | 11.0 (3.7–18.2) | 1 | n.d. | n.d. | 6 |
CDPPB | n.d. | 7.27 (6.79–7.74) | −0.64 (−1.10 to −0.24) | 4 | 1.91 (−0.3 to 4.1) | 0.211 (0.067–0.356) | 4.7 | 6.96 | 6 |
Compound 2c | 5.17 (5.08–5.27)h | 5.36 (5.19–5.53) | −0.96 (−1.17 to −0.75) | 6 | 0.16 (−0.01 to 0.34) | 1 | n.d. | n.d. | 3 |
n.d., not determined due to no fit with the given model.
↵a Negative logarithm of the equilibrium dissociation constant determined with a competitive binding model.
↵b Negative logarithm of the equilibrium dissociation constant determined with an allosteric binding model.
↵c Logarithm of the cooperativity factor.
↵d Association rate constant.
↵e Dissociation rate constant. For ligands with fast koff, global analyses could not derive koff; therefore, the value was constrained to 1 to enable estimation of kon.
↵f RT, residence time defined as 1/koff.
↵g Negative logarithm of the equilibrium dissociation constant determined from kinetic parameters (koff/kon).
↵h Assumed full displacement (=constrained minimum to 0%).